Our overall objectives involve a study of the mechanisms whereby the pulmonary circulation of man and animals is controlled and how these mechanisms are deranged in man living at high altitudes and in patients with acute and chronic lung and heart disease. We wish to discover the major mechanisms of control of this circulation and the intimate intermediate factors which are involved in the control, particularly with regard to the well-known controllers, hypoxia and hypercapnic acidosis. Our technics have utilized studies in the perfused lobes of animals for pharmacologic dose-response curves, isolated strips of pulmonary arterial smooth muscle for both pharmacologic and electro-mechanical studies, investigation in intact man with normal lungs and those with lung disease. We have extended our experience with pulmonary vascular smooth muscle to that of tracheobronchial smooth muscle and glands in order to compare the two pharmacologically; in this manner, it should be possible to ascertain whether the unique performance of the pulmonary vascular smooth muscle is based on its special receptor characteristics, on the humoral milieu in which it resides or on some other special feature.